Polymer fiber tubular structure having kinking resistance

ABSTRACT

An apparatus for forming a tubular structure from a liquefied polymer, the apparatus comprising: (a) a dispenser for dispensing the liquefied polymer; (b) a precipitation electrode being at a first potential relative to the dispenser, the precipitation electrode being designed and constructed for generating a polymeric shell thereupon; and (c) a mechanism for increasing a local density of the polymeric shell in a plurality of predetermined sub-regions of the polymeric shell, thereby to provide a tubular structure having an alternating density in a longitudinal direction.

FIELD AND BACKGROUND OF THE INVENTION

[0001] The present invention relates to a method and apparatus formanufacturing tubular structures via electrospinning and, moreparticularly, to a method and apparatus for manufacturing a polymerfiber tubular structure having improved kinking resistance. The presentinvention further relates to tubular structures having improved kinkingresistance.

[0002] In many medical and industrial applications, tubular structuresmade from polymer fibers are used as, e.g., vascular prostheses, shuntsand the like. Production of polymer fiber tubular structures isparticularly difficult when such tubular structures are required to haveradial tensile strength sufficient to resist tearing and collapse inresponse to a pulsating pressure while at the same time maintain severalelastic properties, such as the ability to bend without breaking andwithout kinking, in order to allow conformation to a complex geometry.

[0003] When an elastic tubular product bends, it experience a finiteforce onto a small surface area, hence the stress concentration at thebending point is high. Consequently, the tubular product is kinked,i.e., it either undergoes destruction, or bends with inner lumencollapse.

[0004] A typical method known in the art to prevent such a collapse isto support the surfaces of the tubular product by rigid circular membersso that the product is made of alternating elastic and rigidlongitudinal sections. Upon axial deformations, the elastic members canfreely operate by tension-compression within the limits admissible bythe agent elastic properties, while at the same time, development ofradial deformations is limited by the presence of the rigid elements.

[0005] Radial support of tubular product can be done in more than oneway. For example, tube corrugation provides alternating sections withdiffering diameter but permanent wall thickness. In this case, requiredrigidity is achieved at the expense of a plurality of wall membersoriented at an angle which is close to 90° relative to the tube centralaxis. Another method is to reinforce an inner or outer wall of anelastic tube, by a rigid spiral pattern made of steel wire or polymerthread of an appropriate diameter. This type of structure can be alsofound in physiological systems such as the tracheal and the bronchial ofthe respiratory system, were rigid cartilage-tissue rings areinterconnected by the elastic connective tissue.

[0006] In the vascular system, blood vessels possess integrity of uniquebiomechanical properties. Of particular importance is the resistance ofthe vessel to inner lumen collapse upon sharp “corners”, which ensuresnormal blood supply.

[0007] Production of tubular fibrous products, including artificialblood vessels, is described in various patents inter alia using thetechnique of electrospinning of liquefied polymer, so that tubularproducts comprising polymer fibers are obtained. Electrospinning is amethod for the manufacture of ultra-thin synthetic fibers, which reducesthe number of technological operations and increases the stability ofproperties of the product being manufactured.

[0008] The process of electrospinning creates a fine stream or jet ofliquid that upon proper evaporation of a solvent or liquid to solidtransition state yield a non-woven structure. The fine stream of liquidis produced by pulling a small amount of polymer solution through spacevia electrical forces. More particularly, the electrospinning processinvolves the subjection of a liquefied polymer substance into anelectric field, whereby the liquid is caused to produce fibers that aredrawn by electric forces to an electrode, and are, in addition,subjected to a hardening procedure. In the case of liquid which isnormally solid at room temperature, the hardening procedure may be merecooling; however other procedures such as chemical hardening(polymerization) or evaporation of solvent may also be employed. Theproduced fibers are collected on a suitably located sedimentation deviceand subsequently stripped of it.

[0009] Artificial vessels made by electrospinning have a number of vitalcharacteristics, including the unique fiber microstructure, in many wayssimilar to that of the natural muscular tissue, high radial complianceand good endothelization ability. However, an artificial vesselfabricated using conventional electrospinning does not withstandkinking, and further reinforcement of the final product is necessary.

[0010] The inner surface of blood vessel prosthesis must be completelysmooth and even so as to prevent turbulence during blood flow andrelated thrombogenesis. This feature prevents the employment of tubecorrugation, since such structure affects the blood flow and may causethrombogenesis. In addition, the vessel rigid members must ensure radialcompliance and, if possible, have fiber structure and porosity similarto that of the basic material of the prosthesis wall. Still in addition,the rigid members should under no conditions be separated from theelastic portions of the prosthesis. On the other hand, in the vascularsystem, application of various adhesives is highly undesirable. Hence,the above mentioned techniques, to prevent collapse of the vessel lumenare inapplicable.

[0011] There is thus a widely recognized need for, and it would behighly advantageous to have, a method and apparatus for manufacturingtubular structures, and particularly vascular prostheses, devoid of theabove limitations.

SUMMARY OF THE INVENTION

[0012] According to one aspect of the present invention there isprovided an apparatus for forming a tubular structure from a liquefiedpolymer, the apparatus comprising: (a) a dispenser for dispensing theliquefied polymer; (b) a precipitation electrode being at a firstpotential relative to the dispenser, the precipitation electrode beingdesigned and constructed for generating a polymeric shell thereupon; and(c) a mechanism for increasing a local density of the polymeric shell ina plurality of predetermined sub-regions of the polymeric shell, therebyto provide a tubular structure having an alternating density in alongitudinal direction.

[0013] According to further features in preferred embodiments of theinvention described below the mechanism for increasing the local densitycomprises a pressing mechanism.

[0014] According to still further features in the described preferredembodiments the mechanism for increasing the local density comprises aplurality of rollers spaced apart from one another.

[0015] According to still further features in the described preferredembodiments the mechanism for increasing the local density comprises aspiral pattern.

[0016] According to still further features in the described preferredembodiments the mechanism for increasing the local density comprises arigid irregular pattern.

[0017] According to still further features in the described preferredembodiments the dispenser is operable to move along the precipitationelectrode.

[0018] According to still further features in the described preferredembodiments the apparatus further comprising a reservoir for holding theliquefied polymer.

[0019] According to still further features in the described preferredembodiments the apparatus further comprising a subsidiary electrodebeing at a second potential relative to the dispenser, and being formodifying an electric field generated between the precipitationelectrode and the dispenser.

[0020] According to still further features in the described preferredembodiments the subsidiary electrode serves for reducingnon-uniformities in the electric field.

[0021] According to still further features in the described preferredembodiments the subsidiary electrode serves for controlling fiberorientation of the tubular structure formed upon the precipitationelectrode.

[0022] According to still further features in the described preferredembodiments the subsidiary electrode is operative to move along theprecipitation electrode.

[0023] According to still further features in the described preferredembodiments the subsidiary electrode is tilted at angle with respect tothe precipitation electrode.

[0024] According to still further features in the described preferredembodiments the apparatus further comprising a mechanism forintertwining at least a portion of a plurality of polymer fibersdispensed by the dispenser, so as to provide at least one polymer fiberbundle moving in a direction of the precipitation electrode.

[0025] According to still further features in the described preferredembodiments the mechanism for intertwining at least a portion of theplurality of polymer fibers comprises a system of electrodes, beinglaterally displaced from the dispenser, being at a third potentialrelative to the dispenser and capable of providing an electric fieldhaving at least one rotating component around a first axis definedbetween the dispenser and the precipitation electrode.

[0026] According to still further features in the described preferredembodiments the system of electrodes includes at least one rotatingelectrode, operable to rotate around the first axis.

[0027] According to still further features in the described preferredembodiments the dispenser and the at least one rotating electrode areoperative to independently move along the precipitation electrode.

[0028] According to still further features in the described preferredembodiments the dispenser and the at least one rotating electrode areoperative to synchronically move along the precipitation electrode.

[0029] According to another aspect of the present invention there isprovided a method of forming a tubular structure from a liquefiedpolymer, the method comprising: (a) via electrospinning, dispensing theliquefied polymer from a dispenser in a direction of a precipitationelectrode, hence forming polymeric shell; and (b) increasing a localdensity of the polymeric shell in a plurality of predeterminedsub-regions of the polymeric shell, thereby providing a tubularstructure having an alternating density in a longitudinal direction.

[0030] According to further features in preferred embodiments of theinvention described below, the method further comprising independentlyrepeating the steps (a) and (b) at least once.

[0031] According to still further features in the described preferredembodiments increasing the local density is done by applying pressureonto the predetermined sub-regions of the polymeric shell.

[0032] According to still further features in the described preferredembodiments increasing the local density is done by pressing a pluralityof rollers, spaced apart from one another, onto the polymeric shell.

[0033] According to still further features in the described preferredembodiments increasing the local density is done by pressing a spiralpattern onto the polymeric shell.

[0034] According to still further features in the described preferredembodiments increasing said local density is done by pressing a rigidirregular pattern onto said polymeric shell.

[0035] According to still further features in the described preferredembodiments the method further comprising mixing the liquefied polymerwith a charge control agent prior to the step of dispensing.

[0036] According to still further features in the described preferredembodiments the method further comprising reducing non-uniformities inan electric field generated between the precipitation electrode and thedispenser.

[0037] According to still further features in the described preferredembodiments reducing non-uniformities in the electric field is done bypositioning a subsidiary electrode, being at a second potential relativeto the precipitation electrode, close to the precipitation electrode.

[0038] According to still further features in the described preferredembodiments the method further comprising controlling fiber orientationof the tubular structure formed upon the precipitation electrode.

[0039] According to still further features in the described preferredembodiments controlling fiber orientation is done by positioning asubsidiary electrode, being at a second potential relative to theprecipitation electrode, close to the precipitation electrode.

[0040] According to still further features in the described preferredembodiments the method further comprising moving the subsidiaryelectrode along the precipitation electrode.

[0041] According to still further features in the described preferredembodiments the method further comprising tilting the subsidiaryelectrode at angle with respect to the precipitation electrode.

[0042] According to still further features in the described preferredembodiments the method further comprising entangling at least a portionof a plurality of polymer fibers dispensed by the dispenser, so as toprovide at least one polymer fiber bundle moving in a direction of theprecipitation electrode.

[0043] According to still further features in the described preferredembodiments the step of entangling comprises providing an electric fieldhaving at least one rotating component around a first axis definedbetween the precipitation electrode and the dispenser.

[0044] According to still further features in the described preferredembodiments providing an electric field having at least one rotatingcomponent, is done by providing a system of electrodes, being laterallydisplaced from the dispenser, being at a third potential relative to theprecipitation electrode and operable to provide a time-dependentelectric field.

[0045] According to still further features in the described preferredembodiments providing an electric field having at least one rotatingcomponent, is done by providing at least one rotating electrode, beinglaterally displaced from the dispenser, being at a third potentialrelative to the precipitation electrode and operable to rotate aroundthe first axis.

[0046] According to still further features in the described preferredembodiments the method further comprising independently moving thedispenser and the at least one rotating electrode along theprecipitation electrode.

[0047] According to still further features in the described preferredembodiments the method further comprising synchronically moving thedispenser and the at least one rotating electrode along theprecipitation electrode.

[0048] According to still further features in the described preferredembodiments the precipitation electrode comprises at least one rotatingmandrel.

[0049] According to still further features in the described preferredembodiments the dispenser comprises a mechanism for forming a jet of theis liquefied polymer.

[0050] According to still further features in the described preferredembodiments the mechanism for forming a jet of the liquefied polymerincludes a dispensing electrode.

[0051] According to still further features in the described preferredembodiments the subsidiary electrode is of a shape selected from thegroup consisting of a plane, a cylinder, a torus and a wire.

[0052] According to yet another aspect of the present invention there isprovided a tubular structure, comprising at least one layer ofelectrospun polymer fibers, each layer having a predetermined porosityand an alternating density in a longitudinal direction of the tubularstructure.

[0053] According to further features in preferred embodiments of theinvention described below, the tubular structure is sized and havingproperties so as to serve as a vascular prosthesis.

[0054] According to still another aspect of the present invention thereis provided a vascular prosthesis, comprising at least one layer ofelectrospun polymer fibers, each layer having a predetermined porosityand an alternating density in a longitudinal direction of the vascularprosthesis.

[0055] According to further features in preferred embodiments of theinvention described below, the polymer is a biocompatible polymer.

[0056] According to still further features in the described preferredembodiments the polymer is selected from the group consisting ofpolyethylene terephtalat and polyurethane.

[0057] According to still further features in the described preferredembodiments said at least one layer includes at least one drugincorporated therein, for delivery of the at least one drug into a bodyvasculature during or after implantation of the vascular prosthesiswithin the body vasculature.

[0058] According to still further features in the described preferredembodiments the electrospun polymer fibers are a combination of abiodegradable polymer and a biostable polymer.

[0059] The present invention successfully addresses the shortcomings ofthe presently known configurations by providing an electrospinningapparatus and method capable of improving kinking resistance of tubularstructures produced thereby.

BRIEF DESCRIPTION OF THE DRAWINGS

[0060] The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

[0061] In the drawings:

[0062]FIG. 1 is a schematic illustration of a prior art electrospinningapparatus;

[0063]FIG. 2 is a schematic illustration of an apparatus for forming atubular structure from a liquefied polymer, according to one embodimentof the present invention;

[0064]FIG. 3a is a mechanism for increasing a local density of thepolymeric shell embodied as a plurality of rollers, according to thepresent invention;

[0065]FIG. 3b is the mechanism for increasing a local density of thepolymeric shell embodied as a spiral pattern, according to the presentinvention;

[0066]FIG. 3c is the mechanism for increasing a local density of thepolymeric shell embodied as a rigid irregular pattern, according to thepresent invention;

[0067]FIG. 4 is a schematic illustration of the apparatus for forming atubular structure further comprising a subsidiary electrode, accordingto the present invention;

[0068]FIG. 5 is a schematic illustration of the apparatus for forming atubular structure further comprising a mechanism for intertwining atleast a portion of the polymer fibers, according to the presentinvention;

[0069]FIG. 6 is a schematic illustration of the intertwining mechanismin the form of a plurality of stationary electrodes, according to thepresent invention;

[0070]FIG. 7 is a schematic illustration of the intertwining mechanismin the form of at least one rotating electrodes, according to thepresent invention.

[0071]FIG. 8a is a tubular structure having toroidal pattern of highdensity regions, according to the present invention;

[0072]FIG. 8b is a tubular structure having spiral-like pattern of highdensity regions, according to the present invention; and

[0073]FIG. 8c is a tubular structure having irregular pattern of highdensity regions, according to the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0074] The present invention is of a method and apparatus for forming atubular structure which can be for example an artificial blood vessel.

[0075] Specifically, the present invention can be used to fabricate atubular structure having an improved kinking resistance.

[0076] For purposes of better understanding the present invention, asillustrated in FIGS. 2-8 of the drawings, reference is first made to theconstruction and operation of a conventional (i.e., prior art)electrospinning apparatus as illustrated in FIG. 1.

[0077]FIG. 1 illustrates an apparatus for manufacturing a non-wovenmaterial using electrospinning, which is referred to herein as apparatus10.

[0078] Apparatus 10 includes a dispenser 12 which can be, for example, areservoir provided with one or more capillary apertures 14. Dispenser 12serves for storing the polymer to be spun in a liquid form, i.e.,dissolved or melted. Dispenser 12 is positioned at a predetermineddistance from a precipitation electrode 16. Precipitation electrode 16serves for forming the tubular structure thereupon. Precipitationelectrode 16 is typically manufactured in the form of a mandrel or anyother substantially cylindrical structure. Precipitation electrode 16 isrotated by a mechanism such that a tubular structure is formed whencoated with the polymer. Dispenser 12 is typically grounded, whileprecipitation electrode 16 is connected to a source of high voltage,preferably of negative polarity, thus forming an electric field betweendispenser 12 and precipitation electrode 16. Alternatively,precipitation electrode 16 can be grounded while dispenser 12 isconnected to a source of high voltage, preferably with positivepolarity.

[0079] To generate a tubular structure, a liquefied polymer (e.g.,melted polymer or dissolved polymer) is extruded, for example under theaction of hydrostatic pressure, or using a pump (not shown in FIG. 1),through capillary apertures 14 of dispenser 12. As soon as meniscus ofthe extruded liquefied polymer forms, a process of solvent evaporationor cooling starts, which is accompanied by the creation of capsules witha semi-rigid envelope or crust. An electric field, occasionallyaccompanied by a unipolar corona discharge in the area of dispenser 12,is generated by the potential difference between dispenser 12 andprecipitation electrode 16. Because the liquefied polymer possesses acertain degree of electrical conductivity, the above-described capsulesbecome charged. Electric forces of repulsion within the capsules lead toa drastic increase in hydrostatic pressure. The semi-rigid envelopes arestretched, and a number of point micro-ruptures are formed on thesurface of each envelope leading to spraying of ultra-thin jets ofliquefied polymer from dispenser 12.

[0080] Under the effect of a Coulomb force, the jets depart fromdispenser 12 and travel towards the opposite polarity electrode, i.e.,precipitation electrode 16. Moving with high velocity in theinter-electrode space, the jet cools or solvent therein evaporates, thusforming fibers which are collected on the surface of precipitationelectrode 16.

[0081] Tubular structure formed in a typical electrospinning process(e.g., as employed by apparatus 10 ), lack sufficient kinking resistanceand further reinforcement of the final product is often necessary tosupport the lumen of the tubular structure while bending. According tothe present invention there is provided an apparatus for forming atubular structure having an intrinsic kinking resistance (i.e. withoutadditional supporting elements).

[0082] Before explaining at least one embodiment of the invention indetail, it is to be understood that the invention is not limited in itsapplication to the details of construction and the arrangement of thecomponents set forth in the following description or illustrated in thedrawings. The invention is capable of other embodiments or of beingpracticed or carried out in various ways. Also, it is to be understoodthat the phraseology and terminology employed herein is for the purposeof description and should not be regarded as limiting.

[0083] Referring now again to the drawings, FIG. 2 illustrates anapparatus, generally referred to herein as apparatus 20, for forming atubular structure from a liquefied polymer according to the teachings ofthe present invention. Apparatus 20 includes a dispenser 21 fordispensing the liquefied polymer, and a precipitation electrode 22 beingat a first potential relative to dispenser 21. Precipitation electrode22 serves for generating a polymeric shell thereupon. Apparatus 20further includes a mechanism 26 for increasing a local density of thepolymeric shell in a plurality of predetermined sub-regions of thepolymeric shell, thereby to provide a tubular structure having analternating density in a longitudinal direction.

[0084] Dispenser 21 is preferably at a first potential relative todispenser 21. According to a preferred embodiment of the presentinvention, dispenser 21 may be operable to move along precipitationelectrode 22, so as to ensure complete or predetermined covering ofprecipitation electrode 22. In addition, precipitation electrode 22 ispreferably operable to rotate around a longitudinal axis.

[0085] The operations of dispenser 21 and precipitation electrode 22 toform a polymeric shell are similar to the operations of dispenser 12 andprecipitation electrode 16 of apparatus 10, as detailed hereinabove. Theposition and size of, and the material from which mechanism 26 is madeof are all selected to ensure that precipitation electrode 22 shieldsmechanism 26, hence minimize any change in the electric field due to thenearby presence mechanism 26. Mechanism 26 is preferably grounded.

[0086] According to a preferred embodiment of the present invention,mechanism 26 may be any device capable of locally increasing the densityof the polymer fibers. Specifically, mechanism 26 may be a pressingmechanism, so that the polymer fibers, being pressed by mechanism 26,are efficiently stuck together forming a rigid and denserthree-dimensional structure. Such condensation results in a certainreduction of electrical resistance in the condensed area and acorresponding intensification of fiber deposition thereat in subsequentelectrospinning steps.

[0087] Reference is now made to FIGS. 3a-c showing three alternativesfor mechanism 26. In FIG. 3a, mechanism 26 is embodied as a plurality ofrollers 32 spaced apart from one another. Rollers 32 are connected to anaxle 34 and operable to freely rotate about axle 34. In FIG. 3b,mechanism 26 is embodied as a rigid spiral pattern 36, operable torotate about a longitudinal axis 38. In FIG. 3c, mechanism 26 isembodied as a rigid irregular pattern 37, operable to rotate about alongitudinal axis 38.

[0088] In the preferred embodiment in which mechanism 26 is a spiral,longitudinal forces are present between mechanism 26 and precipitationelectrode 22. Hence, according to a preferred embodiment of the presentinvention, mechanism 26 may be operable to move along longitudinal axis38, so as to prevent smearing of the compressed sub-regions ofprecipitation electrode 22. It should be understood, that the length ofmechanism 26 is chosen so that a predetermined length of the producedtubular shell is in contact with mechanism 26.

[0089] The rotation of mechanism 26 may be either free rotation orforced rotation, by the use of a rotating device 39. According to apreferred embodiment of the present invention, mechanism 26 may beeither in inactive mode, i.e. detached from precipitation electrode 22,or in active mode i.e. when mechanism 26 (either embodied as rollers 32or as spiral pattern 36) is pressed against precipitation electrode 22.Whether or not mechanism 26 is connected to rotating device 39, whenmechanism 26 is in its active mode, the relative transverse velocitybetween precipitation electrode 22 and mechanism 26 should besynchronized to substantially zero, so as to ensure a rolling withoutsliding motion. Once mechanism 26 is pressed onto precipitationelectrode 22, denser three dimensional patterns start to appear on thesurface of the formed tubular structure, which patterns depend on theshape and size of mechanism 26 as shown in FIGS. 3a-c.

[0090] Apparatus 20 described hereinabove can be efficiently used forgenerating tubular structures upon a precipitation electrode having orlarge radius of curvature. However, when using a precipitation electrodebeing at least partially with small radius of curvature, the orientationof the electric field maximal strength vector is such that precipitationelectrode 22 is coated coaxially by the fibers. Thus, small diameterproducts, may exhibit limited radial strength.

[0091] In cases where precipitation electrode 22 comprises sharp edgesand/or variously shaped and sized recesses, the electric field magnitudein the vicinity of precipitation electrode 22 may exceed the airelectric strength (about 30 kV/cm), and a corona discharge may developin the area of precipitation electrode 22. The effect of coronadischarge decreases the coating efficiency of the process as furtherdetailed herein.

[0092] Corona discharge initiation is accompanied by the generation of aconsiderable amount of air ions having opposite charge sign with respectto the charged fibers. Since an electric force is directed with respectto the polarity of charges on which it acts, theses ions start to moveat the opposite direction to fibers motion i.e., from precipitationelectrode 22 towards dispenser 24. Consequently, a portion of these ionsgenerate a volume charge (ion cloud), non-uniformly distributed in theinter-electrode space, thereby causing electric field lines to partiallyclose on the volume charge rather than on precipitation electrode 22.Moreover, the existence of an opposite volume charges in theinter-electrode space, decreases the electric force on the fibers, thusresulting in a large amount of fibers accumulating in theinter-electrode space. Such an effect may lead to a low-efficiencyprocess of fiber coating, and may even result in a total inability offibers to be collected upon precipitation electrode 22.

[0093] The present invention successfully addresses both of the aboveproblems, by providing a subsidiary electrode within apparatus 20, so asto control the electric field. Specifically, a subsidiary electrode mayeither substantially decreases non-uniformities in the electric fieldand/or provides for controlled fiber orientation upon deposition.

[0094] Reference is now made to FIG. 4, which depicts another preferredembodiment of the present invention, which may be employed forfabricating tubular structures having a small diameter and/orintricate-profile. Hence, apparatus 20 may further comprise a subsidiaryelectrode 46 which is kept at a second potential difference relative todispenser 21. Subsidiary electrode 46 serves for controlling thedirection and magnitude of the electric field in the inter-electrodespace and as such, subsidiary electrode 46 can be used to control theorientation of polymer fibers deposited on precipitation electrode 22.In some embodiments, subsidiary electrode 46 serves as a supplementaryscreening electrode. Broadly stated, use of screening results indecreasing the coating precipitation factor, which is particularlyimportant upon precipitation electrodes having at least a section ofsmall radii of curvature.

[0095] According to a preferred embodiment of the present invention thesize, shape, position and number of subsidiary electrode 46 is selectedso as to maximize the coating precipitation factor, while minimizing theeffect of corona discharge in the area of precipitation electrode 22and/or so as to provide for controlled fiber bundles orientation upondeposition. Thus, subsidiary electrode 46 may be fabricated in a varietyof shapes each serving a specific purpose. Electrode shapes which can beused with apparatus 20 of the present invention include, but are notlimited to, a plane, a cylinder, a torus a rod, a knife, an arc or aring.

[0096] According to a presently preferred embodiment of the invention,subsidiary electrode 46 may be operable to move along precipitationelectrode 22. Such longitudinal motion may be in use when enhancedcontrol over fiber orientation is required. The longitudinal motion ofsubsidiary electrode 46 may be either independent or synchronized withthe longitudinal motion of dispenser 21. Subsidiary electrode 46 mayalso be tilted through an angle of 45°-90° with respect to alongitudinal axis of precipitation electrode 22, which tilting may beused to provide for controlled fiber-bundle orientation upon deposition,specifically, large angles result in predominant polar (transverse)orientation of bundles.

[0097] Depending on the use of the tubular structure formed by apparatus20, it may be required to enhance the strength and/or elasticity, bothin a radial direction and in an axial direction, of the final product.This is especially important when the tubular structure is to be used inmedical applications, where a combination of high elasticity, strength,small thickness, porosity, and low basis weight are required. Accordingto a preferred embodiment of the present invention the strength of thetubular structure may be significantly enhanced, by employing anadditional electric field having at least one rotating element, asdescribed herein.

[0098] Referring to FIG. 5, apparatus 20 further includes a mechanism 52for intertwining at least a portion of the polymer fibers, so as toprovide at least one polymer fiber bundle moving in a direction ofprecipitation electrode 22. Mechanism 52 may include any mechanicaland/or electronic components which are capable for intertwining thepolymer fibers “on the fly”, as is further detailed hereinunder, withreference to FIGS. 6-7.

[0099] Thus, FIG. 6 illustrates one embodiment of the present inventionin which mechanism 52 includes a system of electrodes being laterallydisplaced from dispenser 21 and preferably at a third potential relativeto dispenser 21. According to a preferred embodiment of the presentinvention the system of electrodes may be constructed in any way knownin the art for providing an electric field rotating around a first axis56 defined between said dispenser and said precipitation electrode.

[0100] For example, as shown in FIG. 6, the system of electrodes mayinclude two or more stationary electrodes 62, connected to at least onepower source 64, so that the potential difference between electrodes 62and precipitation electrode 22 (and between electrodes 62 and dispenser21 ) varies in time. Power sources 64, being electronicallycommunicating with each other so as to synchronize a relative phasebetween electrodes 62. Hence, each of stationary electrodes 62 generatesa time-dependent electric field having a constant direction. Theelectronic communication between power sources 64 ensures that the sumof all (time-dependent) field vectors is rotating around first axis 56.

[0101] Reference is now made to FIG. 7, in which mechanism 52 ismanufactured as at least one rotating electrode 72, operable to rotatearound first axis 56. Rotating electrode 72, being at a third potentialrelative to dispenser 21, generates an electric field, the direction ofwhich follows the motion of rotating electrode 72, hence an electricfield having at least one rotating component is generated.

[0102] According to the presently preferred embodiment of the invention,in operation mode of apparatus 20, the liquefied polymer is dispensed bydispenser 24, and then, subjected to the electric field, moves in theinter-electrode space. The electric field in the inter-electrode spacehas at least one rotating component around first axis 56 (generated bythe potential difference between mechanism 52 and precipitationelectrode 22 ) and a stationary electric field (generated by thepotential difference between dispenser 21 and precipitation electrode 22). Hence, in addition to the movement in the direction of precipitationelectrode 22, the jets of liquefied polymer, under the effect of therotating component of the electric field twist around first axis 56. Therotation frequency may be controlled by a suitable choice ofconfiguration for the system of electrodes, as well as on the value ofthe potential differences employed.

[0103] At a given time, the effect of the rotating component of theelectric field on the jets neighboring mechanism 52 is larger than theeffect on the jets which are located far from mechanism 52. Hence, thetrajectories of the fibers start crossing one another, resulting inphysical contacts and entanglement between fibers prior toprecipitation.

[0104] Thus, apparatus 20 generates higher-order formations of fiberbundles from the elementary fibers in the spray jet. The structure ofthe formed fiber bundles is inhomogeneous and depends on the distance ofthe fiber bundle from mechanism 52. Specifically, the extent of fibertwisting and interweaving, and the amount of fibers in the bundle, is anincreasing function of the distance from mechanism 52. During the motionof the bundles in the inter-electrode space, they may also intertwinewith one another, forming yet thicker bundles.

[0105] The bundles, while formed, continue to move in theinter-electrode space, directed to precipitation electrode 22, formingthe tubular structure thereupon. The formed material hasthree-dimensional reticular structure, characterized by a large numberof sliding contacts between fibers. Such contacts significantly increasethe strength of the material, due to friction forces between fibers. Theability of fibers for mutual displacement increases the elasticity ofthe non-woven material under loading.

[0106] According to another aspect of the present invention there isprovided a method for of forming a tubular structure from a liquefiedpolymer. The method comprises the following steps which may be executed,for example, using apparatus 20. Hence, in a first step, the liquefiedpolymer is dispensed via electrospinning from a dispenser in a directionof a precipitation electrode, thus forming a plurality of polymer fibersprecipitated onto the precipitation electrode, hence providing apolymeric shell. In a second step, a local density of the polymericshell is increased in a plurality of predetermined sub-regions of thepolymeric shell. These steps may be subsequent or be implementedsubstantially simultaneously.

[0107] According to a preferred embodiment of the present invention, themethod may further comprise the step of entangling at least a portion ofthe polymer fibers, so as to provide at least one polymer fiber bundlemoving in the direction of the precipitation electrode. In addition, themethod may further comprise a step of controlling fiber and/or fiberbundles orientation of the tubular structure formed upon theprecipitation electrode. Still in addition, the method may comprisereducing undesired non-uniformities in the electric field in thevicinity of the precipitation electrode. The steps of controlling fiberand/or fiber bundles orientation and of reducing non-uniformities in theelectric field may be performed by the use of a subsidiary electrode, asdetailed hereinabove, with reference to FIG. 4.

[0108] It is to be understood, that the second step of the invention isperformed, whether or not the above additional steps of entangling,controlling fiber orientation and reducing electric fieldnon-uniformities have been employed. Furthermore, each of the additionalsteps may be employed independently.

[0109] According to a preferred embodiment of the present invention, themethod may iteratively proceed, so that a multilayer tubular structureis formed. Specifically, once a first layer is formed on theprecipitation electrode, the second step of the method is employed sothat the first layer of the tubular structure is characterized by analternating density in a longitudinal direction. The second step may beemployed, by switching mechanism 26 into active mode, e.g., by movingaxle 34 closer to the precipitation electrode so that rollers 32 arepressed onto the first layer.

[0110] In a subsequent iteration, mechanism 26 is switched into aninactive mode (e.g., by moving axle 34 sufficiently far from theprecipitation electrode) and the electrospinning step is repeated toprovide an additional layer.

[0111] Thus, a multilayer structure is formed, wherein each layer isprovided with a plurality of higher density sections. Reference is nowmade to FIGS. 8a-c, showing three alternatives of the higher densitypatterns formed on a specific layer (for example the first layer) oftubular structure 82. Hence, FIG. 8a illustrates toroidal high densitypatterns formed on tubular structure 82. Such high density patterns maybe provided for example by using a plurality of rollers as the mechanismfor increasing a local density, as detailed hereinabove, and illustratedin FIG. 3a. FIG. 8b illustrates a high density pattern which may beformed by using spiral pattern as a pressing mechanism, as detailedhereinabove, and illustrated in FIG. 3b. Finally, FIG. 3c illustrates anirregular pattern of high density formed onto the surface of tubularstructure 82, which may be patterned by a pressing mechanism shown andin FIG. 3c and described hereinabove.

[0112] It should be appreciated that the high density regions on theouter surface the layers of tubular structure 82, may have anypredetermined pattern (depending on the application in which tubularstructure 82 is to be used), and are not limited to those shown in FIGS.8a-c.

[0113] The tubular structure, which may serve in variety of industrialand medical application, is capable to withstand kinking collapse whilemaintaining a predetermined porosity as well as inner and/or outersurface smoothness. A typical width of the toroidal sections may rangefrom 0.5 to 3 mm.

[0114] According to a preferred embodiment of the present invention, themultilayer structure may be sized and having properties so as to serveas a vascular prosthesis. One advantage of a vascular prosthesis,fabricated in accordance to a preferred embodiment of the presentinvention, is that drug delivery into a body vasculature can beperformed during or after implantation of the vascular prosthesis withinthe body vasculature. Thus, each the layers may incorporate at least onedrug therein, for delivery into body vasculature by, for example, a slowrelease mechanism. It is appreciated that the drug incorporated, as wellas the concentration and method of incorporation into the prosthesis isin accordance with the type of vessel being replaced, and with theparticular pathology of the patient.

[0115] According to a preferred embodiment of the present invention, theliquefied polymer loaded into dispenser 21 may be, for examplepolyurethane, polyester, polyolefin, polymethylmethacrylate, polyvinylaromatic, polyvinyl ester, polyamide, polyimide, polyether,polycarbonate, polyacrilonitrile, polyvinyl pyrrolidone, polyethyleneoxide, poly (L-lactic acid), poly (lactide-CD-glycoside),polycaprolactone, polyphosphate ester, poly (glycolic acid), poly(DL-lactic acid), and some copolymers. Biolmolecules such as DNA, silk,chitozan and cellulose may also be used in mix with synthetic polymers.Improved charging of the polymer may also be required. Improved chargingis effected according to the present invention by mixing the liquefiedpolymer with a charge control agent (e.g., a dipolar additive) to form,for example, a polymerdipolar additive complex which apparently betterinteracts with ionized air molecules formed under the influence of theelectric field. The charge control agent is typically added in the gramsequivalent per liter range, say, in the range of from about 0.001 N toabout 0.1 N, depending on the respective molecular weights of thepolymer and the charge control agent used.

[0116] U.S. Pat. Nos. 5,726,107; 5,554,722; and 5,558,809 teach the useof charge control agents in combination with polycondensation processesin the production of electret fibers, which are fibers characterized ina permanent electric charge, using melt spinning and other processesdevoid of the use of a precipitation electrode. A charge control agentis added in such a way that it is incorporated into the melted orpartially melted fibers and remains incorporated therein to provide thefibers with electrostatic charge which is not dissipating for prolongedtime periods, say weeks or months. In a preferred embodiment of thepresent invention, the charge control agent transiently binds to theouter surface of the fibers and therefore the charge dissipates shortlythereafter. This is because polycondensation is not exercised at allsuch that the chemical interaction between the agent and the polymer isabsent, and further due to the low concentration of charge control agentemployed. The resulting tubular structure is therefore, if so desired,substantially charge free.

[0117] Suitable charge control agents include, but are not limited to,mono- and poly-cyclic radicals that can bind to the polymer moleculevia, for example, —C═C—, ═C—SH— or —CO—NH— groups, including biscationicamides, phenol and uryl sulfide derivatives, metal complex compounds,triphenylmethanes, dimethylmidazole and ethoxytrimethylsians.

[0118] Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following example, which is not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds experimental support in the followingexample.

EXAMPLE

[0119] Reference is now made to the following example, which togetherwith the above descriptions, illustrate the invention in a non limitingfashion.

[0120] Tubular structures, 6 mm in diameter and 200 mm in length weremanufactured.

[0121] A polyurethane of Carbotan 3595 blend was purchased from ThePolymer Technology Group Incorporated. This polymer was provided witharomatic urethane hard segment, polycarbonate and silicone co-softsegments and surface-modifying end groups. Silicone-urethane copolymersdemonstrate a combination of high mechanical properties with oxidativestability, low rate of hydrolytic degradation biostabillity andtromboresistance. In addition, this polymer is characterized by a highfiber forming ability.

[0122] A rod, 6 mm in diameter and 300 mm in length was used as aprecipitation electrode, and its central 200 mm portion was coated atambient temperature (24° C.). The precipitation electrode was rotated atan angular velocity of 100 rpm.

[0123] A spinneret was used as the dispensing electrode, the innerdiameter of the spinneret was 0.5 mm, and the flow-rate was 3 ml/h. Thedispensing electrode was grounded while the precipitation electrode waskept at a potential of −50 kV, relative to the dispensing electrode.

[0124] The dispensing electrode was positioned 35 cm from theprecipitation electrode. Reciprocal motion of the dispensing electrodewas enabled along the mandrel longitudinal axis at a frequency of 5motions per minute.

[0125] An axel connected to a plurality of rollers, spaced apart fromone another, was used as a mechanism for increasing a local density. Thespacing between the rollers was 1.2 mm, and the width of each roller was0.8 mm.

[0126] Four tubular structures were manufactured according to theteaching of the present invention, for each tubular structure adifferent pressure of the rollers onto the mandrel was applied. Theresulting thicknesses of the compressed sub-regions were: 0.5, 0.6, 0.8and 0.9. In addition, for comparison, a tubular structure wasmanufactured employing conventional electrospinning process without thestep of increasing local densities.

[0127] In all the experiments, the parameters of the electrospinningprocess were identical, except for the pressure of the rollers on themandrel.

[0128] The manufactured tubular structures were subjected to bendingtests so as to compare the kinking resistance of the final product, as afunction of the of the compressed sub-regions thicknesses. In addition,global and local measurements of the basis weight were performed foreach of the tubular structures.

[0129] Table 1 lists some comparative characteristics of the tubularstructures produced by a conventional electrospinning technique by theteachings of the present invention. TABLE 1 Wall thickness [mm] Basisweight [g/m²] Critical Non- Non- bending Compressed compressedCompressed compressed radius sub-region sub-region Web sub-regionsub-region [mm] — 0.6 150 — — 25.0 0.5 0.6 200 250 160 7.0 0.6 0.6 290430 150 14.0 0.8 0.6 280 400 150 17.0 0.9 0.8 420 650 220 11.0

[0130] As can be seen from Table 1, the existence of compressedsub-regions on the wall of the tubular structure provides relativelyheavy sub-regions of the structure. In some experiments, intensificationof fiber deposition upon the precipitation electrode in the compressedsub-regions has been observed. This is shown at the bottommost two rowsof Table 1, where the wall thickness at the compressed sub-regions islarger than the “original” wall thickness (i.e. at the non-compressedsub-regions). The observed phenomenon is due to a reduction ofelectrical resistance in the compressed sub-regions.

[0131] These compressed sub-regions, significantly increase the abilityof the structure to bend. The thinner the thickness of the wall at thecompressed subregion, the larger is the kinking resistance of thestructure.

[0132] It is appreciated that certain features of the invention, whichare, for clarity, described in the context of separate embodiments, mayalso be provided in combination in a single embodiment. Conversely,various features of the invention, which are, for brevity, described inthe context of a single embodiment, may also be provided separately orin any suitable subcombination.

[0133] Although the invention has been described in conjunction withspecific embodiments thereof, it is evident that many alternatives,modifications and variations will be apparent to those skilled in theart. Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

What is claimed is:
 1. An apparatus for forming a tubular structure froma liquefied polymer, the apparatus comprising: (a) a dispenser fordispensing the liquefied polymer; (b) a precipitation electrode being ata first potential relative to said dispenser, said precipitationelectrode being designed and constructed for generating a polymericshell thereupon; and (c) a mechanism for increasing a local density ofsaid polymeric shell in a plurality of predetermined sub-regions of saidpolymeric shell, thereby to provide a tubular structure having analternating density in a longitudinal direction.
 2. The apparatus ofclaim 1, wherein said mechanism for increasing said local densitycomprises a pressing mechanism.
 3. The apparatus of claim 1, whereinsaid mechanism for increasing said local density comprises a pluralityof rollers spaced apart from one another.
 4. The apparatus of claim 1,wherein said mechanism for increasing said local density comprises aspiral pattern.
 5. The apparatus of claim 1, wherein said mechanism forincreasing said local density comprises a rigid irregular pattern. 6.The apparatus of claim 1, wherein said precipitation electrode comprisesat least one rotating mandrel.
 7. The apparatus of claim 1, wherein saiddispenser is operable to move along said precipitation electrode.
 8. Theapparatus of claim 1, wherein said dispenser comprises a mechanism forforming a jet of the liquefied polymer.
 9. The apparatus of claim 8,wherein said mechanism for forming a jet of the liquefied polymerincludes a dispensing electrode.
 10. The apparatus of claim 1, furthercomprising a reservoir for holding the liquefied polymer.
 11. Theapparatus of claim 1, further comprising a subsidiary electrode being ata second potential relative to said dispenser, and being for modifyingan electric field generated between said precipitation electrode andsaid dispenser.
 12. The apparatus of claim 11, wherein said subsidiaryelectrode serves for reducing non-uniformities in said electric field.13. The apparatus of claim 11, wherein said subsidiary electrode servesfor controlling fiber orientation of the tubular structure formed uponsaid precipitation electrode.
 14. The apparatus of claim 11, whereinsaid subsidiary electrode is of a shape selected from the groupconsisting of a plane, a cylinder, a torus and a wire.
 15. The apparatusof claim 11, wherein said subsidiary electrode is operative to movealong said precipitation electrode.
 16. The apparatus of claim 11,wherein said subsidiary electrode is tilted at angle with respect tosaid precipitation electrode.
 17. The apparatus of claim 1, furthercomprising a mechanism for intertwining at least a portion of aplurality of polymer fibers dispensed by said dispenser, so as toprovide at least one polymer fiber bundle moving in a direction of saidprecipitation electrode.
 18. The apparatus of claim 17, wherein saidmechanism for intertwining at least a portion of said plurality ofpolymer fibers comprises a system of electrodes, being laterallydisplaced from said dispenser, being at a third potential relative tosaid dispenser and capable of providing an electric field having atleast one rotating component around a first axis defined between saiddispenser and said precipitation electrode.
 19. The apparatus of claim18, wherein said system of electrodes includes at least one rotatingelectrode, operable to rotate around said first axis.
 20. The apparatusof claim 19, wherein said dispenser and said at least one rotatingelectrode are operative to independently move along said precipitationelectrode.
 21. The apparatus of claim 19, wherein said dispenser andsaid at least one rotating electrode are operative to synchronicallymove along said precipitation electrode.
 22. A method of forming atubular structure from a liquefied polymer, the method comprising: (a)via electrospinning, dispensing the liquefied polymer from a dispenserin a direction of a precipitation electrode, hence forming polymericshell; and (b) increasing a local density of said polymeric shell in aplurality of predetermined sub-regions of said polymeric shell, therebyproviding a tubular structure having an alternating density in alongitudinal direction.
 23. The method of claim 22, further comprisingindependently repeating said steps (a) and (b) at least once.
 24. Themethod of claim 22, wherein said increasing said local density is doneby applying pressure onto said predetermined sub-regions of saidpolymeric shell.
 25. The method of claim 22, wherein said increasingsaid local density is done by pressing a plurality of rollers, spacedapart from one another, onto said polymeric shell.
 26. The method ofclaim 22, wherein said increasing said local density is done by pressinga spiral pattern onto said polymeric shell.
 27. The method of claim 22,wherein said increasing said local density is done by pressing a rigidirregular pattern onto said polymeric shell.
 28. The method of claim 22,further comprising mixing the liquefied polymer with a charge controlagent prior to said step of dispensing.
 29. The method of claim 28,wherein said dispenser being at a first potential relative to saidprecipitation electrode.
 30. The method of claim 22, wherein saiddispenser comprises a mechanism for forming a jet of the liquefiedpolymer.
 31. The method of claim 30, wherein said mechanism for forminga jet of the liquefied polymer includes a dispensing electrode.
 32. Themethod of claim 22, further comprising reducing non-uniformities in anelectric field generated between said precipitation electrode and saiddispenser.
 33. The method of claim 32, wherein said reducingnon-uniformities in said electric field is done by positioning asubsidiary electrode, being at a second potential relative to saidprecipitation electrode, close to said precipitation electrode.
 34. Themethod of claim 22, further comprising controlling fiber orientation ofthe tubular structure formed upon said precipitation electrode.
 35. Themethod of claim 34, wherein said controlling fiber orientation is doneby positioning a subsidiary electrode, being at a second potentialrelative to said precipitation electrode, close to said precipitationelectrode.
 36. The method of claim 33, wherein said subsidiary electrodeis of a shape selected from the group consisting of a plane, a cylinder,a torus and a wire.
 37. The method of claim 35, wherein said subsidiaryelectrode is of a shape selected from the group consisting of a plane, acylinder, a torus and a wire.
 38. The method of claim 33, furthercomprising moving said subsidiary electrode along said precipitationelectrode.
 39. The method of claim 35, further comprising moving saidsubsidiary electrode along said precipitation electrode.
 40. The methodof claim 33, further comprising tilting said subsidiary electrode atangle with respect to said precipitation electrode.
 41. The method ofclaim 35, further comprising tilting said subsidiary electrode at anglewith respect to said precipitation electrode.
 42. The method of claim22, further comprising entangling at least a portion of a plurality ofpolymer fibers dispensed by said dispenser, so as to provide at leastone polymer fiber bundle moving in a direction of said precipitationelectrode.
 43. The method of claim 41, wherein said step of entanglingcomprises providing an electric field having at least one rotatingcomponent around a first axis defined between said precipitationelectrode and said dispenser.
 44. The method of claim 43, wherein saidproviding an electric field having at least one rotating component, isdone by providing a system of electrodes, being laterally displaced fromsaid dispenser, being at a third potential relative to saidprecipitation electrode and operable to provide a time-dependentelectric field.
 45. The method of claim 43, wherein said providing anelectric field having at least one rotating component, is done byproviding at least one rotating electrode, being laterally displacedfrom said dispenser, being at a third potential relative to saidprecipitation electrode and operable to rotate around said first axis.46. The method of claim 45, further comprising independently moving saiddispenser and said at least one rotating electrode along saidprecipitation electrode.
 47. The method of claim 45, further comprisingsynchronically moving said dispenser and said at least one rotatingelectrode along said precipitation electrode.
 48. A tubular structure,comprising at least one layer of electrospun polymer fibers, each layerhaving a predetermined porosity and an alternating density in alongitudinal direction of the tubular structure.
 49. The tubularstructure of claim 48, sized and having properties so as to serve as avascular prosthesis.
 50. The tubular structure of claim 48, wherein saidelectrospun polymer fibers are biocompatible.
 51. The tubular structureof claim 48, wherein said electrospun polymer fibers are selected fromthe group consisting of polyethylene terephtalat fibers and polyurethanefibers.
 52. The tubular structure of claim 48, wherein at least one ofsaid at least one layer includes at least one drug incorporated therein,for delivery of said at least one drug into a body vasculature during orafter implantation of the tubular structure within said bodyvasculature.
 53. The tubular structure of claim 52, wherein saidelectrospun polymer fibers are a combination of a biodegradable polymerand a biostable polymer.
 54. A vascular prosthesis, comprising at leastone layer of electrospun polymer fibers, each layer having apredetermined porosity and an alternating density in a longitudinaldirection of the vascular prosthesis.
 55. The vascular prosthesis ofclaim 54, wherein said electrospun polymer fibers are biocompatible. 56.The vascular prosthesis of claim 54, wherein said electrospun polymerfibers are selected from the group consisting of polyethyleneterephtalat fibers and polyurethane fibers.
 57. The vascular prosthesisof claim 54, wherein at least one of said at least one layer includes atleast one drug incorporated therein, for delivery of said at least onedrug into a body vasculature during or after implantation of thevascular prosthesis within said body vasculature.
 58. The vascularprosthesis of claim 57, wherein said electrospun polymer fibers are acombination of a biodegradable polymer and a biostable polymer.